Acquired immunodeficiency syndrome (AIDS) is currently a life-threatening epidemic of global concern. It is of pressing need to develop effective vaccines to induce active immunity in the individuals at risk to the infection. Based on the phenomena of idiotype (Id) networks in antibody- mediated immune responses, we now propose the use of HIV-1 group-specific neutralizing monoclonal antibodies (Mabs) to generate monoclonal anti- idiotypic antibodies (anti-Ids) which mimic the neutralization epitopes of the virus. The long-term objective of the project is to develop safe and effective anti-Id vaccines to protect the population from the disease. The specific aims of this Phase II project are: (1) to further characterize the serological properties of the two anti-Ids (AB19-4 and AB19-31) generated in our Phase I study, (2) to generate additional anti- Ids from a Mab recognizing the conserved CD4-binding region on HIV-1 gp 120, (3) to examine the in vivo effect of the anti-Ids on the generation of Ab-3 responses in mice and rabbits, (4) to examine Ab-3 responses in regard to anti-gp120 activity and HIV-1 neutralization induced byu a cocktail of the anti-Ids in mice and rabbits, and (5) to further examine these Ab-3 responses in primates (baboons).